Present position and address



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Research project supervision


I have supervised a large number of research projects in the field of Pharmacognosy, undertaken by BPharm, MPharm, MSc, and Summer Vacation students as well as over 30 dissertations (written literature surveys) by undergraduate and MSc students. This is in addition to the PhD projects described in Section V.
The projects have covered the following areas:

  • literature surveys on the pharmacognosy of particular plants

  • literature surveys on plants used for particular disease areas

  • commercial, legislative and analytical aspects of botanical medicines

  • development of monographs for botanical medicines

  • phytochemical analysis and isolation

  • bioassays on medicinal plants

  • questionnaire based surveys on pharmaceutical care of vitiligo patients.



Teaching activities outside formal departmental commitments:

  • One-day workshop on HPLC and GLC for students of the MSc in Biomedical Research.

  • One-day postgraduate training workshop for PhD students on natural product isolation.

  • “Separation methods” lectures to Intercalated BSc medical students at St Thomas’ Hospital

  • Lectures on “What is pharmacognosy?” to students of Traditional Chinese Medicine at the Middlesex University, Enfield

  • Supervision of projects on medicinal plants for non-King’s university students (several)

  • A one- week course, for external students from the herbal industry, on “Evaluation of medicinal plants” (1994).

  • Talks on botanical medicines to local branches of the Royal Pharmaceutical Society of Great Britain.



Effectiveness of Educational Activity:

The quality of my teaching and impression on students has been evaluated and proved excellent by:



  • Success of final year elective courses in Pharmacognosy: These courses changed dramatically from being unpopular units in 1990 to oversubscribed electives in the last few years. The numbers of students enlisting for these two courses (“Plants and Pharmacy” and “Drug Discovery from Natural Sources”) increased from about 2 or 3 to over 20 students in each elective course. This also reflects the success of the compulsory penultimate-year pharmacognosy course which has clearly stimulated the students to pursue the subject as a specialisation in their final year.

  • Formal questionaires issued at the end of courses: From student responses, my lectures are rated as interesting, well organized, easy to follow and clear. Average scores of over 75-90% were obtained for these parameters. Students also reported a high level of satisfaction with the course content. Teaching evaluations from the Behavioral Neuroscience course at OHSU have been similarly complimentary.

  • Coursework reports: The good quality of the coursework reports is an indication of the effectiveness of the teaching during practical classes. The improvement of the weaker students’ performance over the year is a marker of the constructive feedback given when grading the reports.

  • Examinations: A large number of students attempt my questions in examinations. As the marks are generally well distributed over a normal range, I am confident that this is because they find my lectures clear, and tempting to revise, rather than because they find the questions easy. (In the UK each examination paper contains questions based on lectures given by a number of different faculty members who all contribute to a particular course rather than each faculty member setting their own course and paper).

  • Enthusiasm of students: The high standard of coursework reports so far, and the general level of interest and enthusiasm of the students has been a positive indication of the success of the pharmacognosy courses.

  • Relationship with students: Students report that they find me approachable and willing to help them with difficulties during and outside formal classes.


Service and Membership of Educational Committees:

The committees on which I have served that had a role in designing courses or general educational structure are:



  • Topic Week Co-ordinator (1992- 1996)

  • Member of the Departmental Undergraduate Committee (1992-1997)

  • Member of a working group revising the MPharm syllabus (2001-2002)

  • Chair of the group designing the induction course for the new MPharm course (2002)


Collaborative Skills:

UK courses involve a group of faculty members working together to teach a course which has been put together by a course organizer. I have successfully organized a special course known as a Topic Week. In this course, faculty from all departments teach, in turn, on their field regarding a particular topic e.g. analgesics are covered from their discovery all the way to patient counseling. I was involved in co-ordinating the discussions and setting up of the induction program and coursework for the new Pharmacy undergraduate intake. My most extensive, successful and on-going collaboration in the educational area has been the development of the Pharmacognosy curriculum at King’s College London in collaboration with Professor Houghton, Professor of Pharmacognosy (now Emeritus).



V. SCHOLARSHIP
Area(s) of Research/Scholarly Interest:
V/1 Summary of Main Research Interests

Since 1990, I have built up an active research programme and a growing international reputation in the field of botanicals with therapeutic potential, focused mainly on the disease targets diabetes, vitiligo and psoriasis. My present role at OHSU involves the scientific evaluation of botanicals and botanically derived products in neurological disorders. This work has expanded to projects involving both pre-clinical and clinical studies on botanical products.


My core expertise is in the “bioassay-guided fractionation” of plants used in traditional medicine as well as development of methods for their quality control. The isolation and structure elucidation of phytochemicals, as well as many biological assays are within my field of expertise. However, the work is necessarily multidisciplinary and I have developed and utilised an extensive range of national and international collaborations in both academia and industry to obtain advice on and training in the biological assays. Details are given under the various subsections describing my research.
My research project on natural products for vitiligo is a unique line of research worldwide and my expertise in traditional anti-diabetic plants is also acknowledged at an international level. I was approached by the drug company, Stiefel, to advise them on the investigation of natural products for psoriasis, and obtained funding for contract work, one postodoctoral scientist and one PhD student from this company. The work has resulted in the filing of national and international patents. OHSU acquired these patents in 2006 from King’s College London and in January 2008, we licensed the patents to a small business, AdPharma. We are on the verge of initiating clinical studies on piperine in vitiligo.
While at King’s College London, I recruited at least one PhD student annually in addition to a number of Masters, Undergraduate, Exchange Scheme and Summer Vacation students each year. I contributed significantly to the development of the Pharmacognosy Research Group at King’s College London. This consisted of only one PhD student in 1990, but in 2002 was the largest Pharmacognosy group in any UK university, and rapidly obtained an international reputation. I have supervised four completed PhD doctoral research projects. In 2002, when I left King’s College I was supervising 4 further PhD students, two postdoctoral researchers, one research assistant and several MSc, MPharm and BSc projects. At OHSU, I have mentored several research assistants, summer students and visiting workers in techniques associated with pharmacognosy.

V/2 Detailed description of research and achievements in the main disease areas

Diabetes

Summary: My team developed a range of simple, mechanism-based in vitro bioassays to test large numbers of plant extracts, fractions and isolated compounds for specific activities useful in treating diabetes e.g. inhibition of intestinal enzymes, inhibition of intestinal glucose uptake and stimulation of pancreatic insulin secretion. The protective role of some natural products against the development of glucose induced diabetic retinopathy is also being examined using models available in the laboratories of Prof Eva Kohner and Dr Rakesh Chibber, St Thomas’s Hospital. A number of interesting compounds showing activity in these in vitro bioassays have been isolated. A 3-year collaboration with the French pharmaceutical company, Lipha led to the isolation of 3 compounds with in vivo anti-diabetic activity from the fruit of Momordica charantia. In 2000, I spent 6 weeks at Merck Research Laboratories in Rahway, NJ learning about more bioassays. Two seminars that I gave on anti-diabetic plants were extremely well received, and the visit resulted in the award of a 3-year collaborative PhD studentship by Merck ($60, 000), beginning January 2001. I also had a joint project on anti-diabetic plant extracts with the Royal Botanic Gardens, Kew, and am an author and editor for a volume on “Anti-diabetic plants” for Harwood publishers (completion due 2004).

Collaborations established: Prof J Timbrell, Dr MJ Lawrence, Dr C Waterfield (Pharmacy, KCL); Dr S Persaud and Dr P Jones (Physiology, KCL); Professor Eva Kohner and Dr Rakesh Chibber (St Thomas’s Hospital, KCL); Dr Paul Skett (Pharmacology, Glasgow); Professor Monique Simmonds (Royal Botanic Gardens, Kew); Prof AD Kinghorn (Pharmacy, Chicago USA); Prof WJ Keller (formerly Pharmacy, Samford, Alabama); Lipha (France) and Merck Research Laboratories (NJ, USA).

Funding: Lipha, EPSRC, The British Council, The Wellcome Trust, Nagai Foundation Japan, American Society of Pharmacognosy, Nuffield Foundation, Merck Research Laboratories.

Outcomes:

  • Publications (see end list):

  • Conference presentations (national and international).

  • Two senior overseas academics spent their sabbatical leave in my laboratory learning and applying the diabetes bioassays we have set up: Dr Molham Al-Habori (Head of Clinical Biochemistry, University of Sana’a, Yemen) and Dr Robin J Marles (Associate Professor of Botany, University of Brandon, Canada).

  • Anti-diabetic plants were selected as an important focus area to attract funding into the Kew-King’s Centre for Bioactivity Screening - a joint venture between King’s College London and the Royal Botanic Gardens Kew.

  • Funding from two major pharmaceutical companies: Lipha and Merck (> £50, 000)

  • Many journals (J. Ethnopharmacol., Phytotherapy Research, Int. J. Pharmacognosy, J. Pharm. Pharmacol.) use my expertise as a referee on papers relating to anti-diabetic plants.

  • Invited editor for a volume on Anti-Diabetic Plants (Harwood Academic Publishers)

  • Award of a European Commision Marie Curie Postdoctoral Fellowship (ca £70, 000) to study plants for diabetic retinopathy. Unfortunately the named candidate was unable to accept the award for family reasons and the award lapsed.

  • Editorship of a book volume on Anti-diabetic plants used worldwide (published 2005).



Psoriasis

Summary: A range of traditional plant remedies for psoriasis, chiefly derived from the Ayurvedic (Indian) and Chinese traditions, have been examined for the ability to inhibit epidermal keratinocyte proliferation in culture or inhibit pro-inflammatory enzymes. Again, my laboratory developed a rapid-throughput assay using keratinocytes supplied by collaborators (Prof. Irene Leigh). The assays were carried out in our department. Dr JRS Hoult carried out tests on our samples using mammalian pro-inflammatory enzymes, while a soya-bean lipoxygenase model is available in house. The initial screening work attracted major funding (about £70, 000) from the company Phytopharm plc, to study in depth the anti-psoriatic potential of a particular plant, Vernonia anthelmintica. An active compound with both anti-proliferant and anti-inflammatory activity was identified. This work received considerable media attention when presented at the British Pharmaceutical Conference in September 2002. Other activities include a link established with Dr Chun-Tao Che in Hong Kong to supply us with samples of authentic Chinese Herbs used for psoriasis. This work was funded by the British Council, which supported a visit by myself to Hong Kong in December 1998, a visit to King’s College by Dr Che in March 1999, and a study visit by a PhD student from my group to Hong Kong in February 1999. Stiefel laboratories (UK) have funded contract work, one PhD student and one postdoctoral researcher to study natural products with potential to treat psoriasis. A USA/India based herbal company (Sabinsa/SAMI labs) also sponsored contract work in our laboratories during 2002.

Collaborations established: Professor Irene Leigh’s group (London Hospital Medical School); Dr JRS Hoult, Pharmacology, KCL; Dr Chun-Tao Che (Chinese University of Hong Kong), Dr CJ Waterfield and Prof J Timbrell (Pharmacy), Phytopharm plc.

Funding: Phytopharm plc, The British Council HK-UK Joint Research Scheme, Stiefel Laboratories, UK, Sabinsa (USA/India).

Outcomes:

  • Publications (see end list).

  • Conference presentations (national and international)

  • Major grants from pharmaceutical companies (>£200, 000)

  • Possible patentable discovery from the Phytopharm sponsored project

  • International collaboration and exchange visits with a Hong Kong based academic

  • Media attention for our successful Vernonia project (access by typing “Raman vernonia psoriasis” into an internet search engine).


Vitiligo

Summary: My group was the only one in the Western world studying traditional plant remedies as a source of novel chemical entities to treat the skin disease vitiligo. The disease, for which no satisfactory treatment exists, is characterised by the absence of pigment cells (melanocytes) in the afflicted patches. My group has developed (and published) a novel rapid-throughput in vitro bioassay to test plants for melanocyte proliferative activity, using pigment cells provided through a collaboration with Professor DC Bennett and Dr P Donatien (St George’s Hospital, London). This work led to the identification of a potent, novel, alkaloidal stimulant for in vitro melanocyte proliferation. National and International patents have been filed (A Raman, Zhixiu Lin, RC Hider and R Venkatasamy as inventors) in co-operation with the British Technology Group. From 2001 – 2003 I was principal investigator for a research group synthesizing analogues of this compound in collaboration with Professor RC Hider (Dept of Pharmacy, KCL) and have received £225,000 from BTG for in vivo studies and further biochemical characterisation of this novel activity in collaboration with Prof. Antony Young (Department of Photobiology, KCL). The results of these studies have been highly successful and have led to the filing of more patents. The work is now ready to enter the clinical stage and will now be overseen by BTG, to whom the patents have been assigned. The scope of the project has expanded considerably beyond the natural products arena; new collaborations have been formed to address these exciting developments. The work has also led to a broadening of my own research expertise and understanding of the drug discovery, patenting and development process.

The patents relating to this project are now owned by OHSU and have been licensed to Adpharma Inc, a US based pharmaceutical company. Along with Adpharma, we will soon be conducting Phase I clinical studies both in India, and here at OHSU along with collaborating dermatologists.



Collaborations established: Professor DC Bennett and Dr P Donatien (St George’s Hospital Medical School, London), Professor Antony Young (St Thomas’s Hospital), Professor RC Hider (Pharmacy, KCL), Adpharma Inc., IL USA, Drs Andrew Blauvelt, Ben Ehst, Theresa Devere and Eric Simpson (Dermatology, OHSU).

Funding: Glaxo, The Vitiligo Society, Institute of Chinese Medicine, British Technology Group; AdPharma Inc.

Outcomes:

  • Publications (see end list)

  • Conference presentations (national and international)

  • Development of a unique and promising line of research

  • A patent for a potential new treatment for vitiligo

  • Investment and support from the British Technology Group (BTG) for commercialisation and for a postdoctoral scientist and research assistant (> £250,000)

  • On-going project possibilities.

  • Membership of the Medical and Research Subcommittee of the Vitiligo Society

  • Consultant to the Vitiligo Society on pharmaceutical matters and those relating to complementary and herbal medicines.

  • Invited speaker at the Vitiligo Symposium, London UK, May 2003.

  • Licensing agreement for OHSU.

  • Significant media and internet attention for this project.



Piperine

Summary:In addition to its effects on pigment cells, piperine is of interest as a chemopreventive agent. We have been performing studies here at OHSU which show that it has opposing effects to TPA, a phorbol ester known to have cancer preventive effects. These studies have been performed using microarray technology, RT-PCR and in vivo in mice.

Collaborations established: Dr Philippe Thuillier (Public Health and Preventive Medicine, OHSU), Dr Steven Jacques (Dermatology and Biomedical Engineering, OHSU).

Funding: Internal funds to date. NIH applications pending.

Outcomes: Collaborations, planned publications

Neurology

Summary: My research in the Neurology Dept began with a career development award within the NIH-funded ORCCAMIND project, PI Professor Barry Oken, Department of Neurology. My project centered on the extraction, evaluation and bioassay-guided fractionation of plants relevant to neurological disorders. I initially screened six herbs (Bacopa monniera, Ginkgo biloba, Uncaria tomentosa, Centella asiatica, Scutellaria laterifolia, Hypericum performatum) used in herbal medicine for neurological conditions. These were tested for effects in neurite elongation and in in vitro screens relevant to Alzheimer’s Disease.
From this pilot study, Centella asiatica has emerged as a plant of significant interest both for Alzheimer’s disease (in collaboration with Dr Joseph Quinn) and for nerve regeneration (in collaboration with Dr Bruce Gold). Preliminary fractionation indicates that a number of active compounds are present which can stimulate neurite elongation in vitro, while whole extracts show promising effects in a sciatic nerve crush model in vivo. This work formed the basis of a successful grant application to NCCAM to study Centella asiatica triterpenes for the treatment of diabetic neuropathy (in collaboration with Dr Jau-Shin Lou). The trial is underway.
I also received two pilot grants to study the role of Centella asiatica in Alzheimer’s disease. Centella asiatica extracts showed benefical activities in in vitro screens relating to amyloid toxicity and in vivo models of Alzheimer’s disease, and this has formed the basis of grant applications to the NIH. These earlier studies were conducted primarily in collaboration with Dr Joseph Quinn and Bruce Gold. However, a recent collaboration has been established with Dr Hemachandra Reddy with a view to study the protective effects of Centella asiatica on mitochondrial function in neurons.
The chemistry and effects (on epilepsy and anxiety) of extracts of Passiflora incarnata in vitro, in vivo and in humans have been examined in collaboration with Dr Siegward Elsas, Dr Jacob Raber and Dr David Rossi (OHSU). I oversaw the development of TLC and HPLC methods to look for Passiflora components both in plant extracts and plasma samples. This data was used to support a successful grant application for a NIH funded K-Award by Dr Siegward Elsas for clinical evaluation of Passiflora in epileptic patients.
I have also been working with Dr Carlo Calabrese (formerly of National College of Natural Medicine) to develop a grant application to the NIH for the investigation of Bacopa monnieri extracts in subjects with mild cognitive impairment. My role in this study will be to characterize the product, conduct stability studies and measure Bacopa components in plasma samples from study participants.
In smaller studies, I have prepared and analysed grape seed extract fractions for use in studies relating to multiple sclerosis and stroke. These preliminary data have also been used in grant applications for further funding. In other studies, I provided independent analysis of a Ginseng product used in a clinical trial in MS patients. The trial was conducted by Drs Laura Schaben, Ruth Whittam and Dennis Bourdette. In collaboration with Dr Peter Spencer, Dr Valerie Palmer, Dr Desire Tshala and Dr Glen Kisby of CROET, I have been studying Cycad and Encephalartos species which are known to have neurotoxic effects in humans. Extracts have been prepared and tested in guinea pigs with a view to investigating purported high molecular weight toxins which have not hitherto been characterized.

Collaborations established: Numerous collaborations have been developed within the OHSU to develop projects based on the neurological effects of botanical medicines. Specific collaborators are listed in the section above.

Funding: The above projects have been funded by a career development award within the NIH/NCCAM-supported (NIH P50 AT00066) ORCCAMIND project, bridge funding from the Department of Neurology, the Oregon Partnership for Alzheimer’s Research, the Oregon Alzheimer’s Disease Center and an NIH/NCCAM supported clinical trial (NIH 1 R21 AT003668-01). I have also been provided with office and, previously, laboratory space in the Center for Research on Occupational and Environmental Toxicology (CROET).

Outcomes:

  • A patent application has been filed for the use of Centella asiatica in nerve regeneration,

  • Publication on nerve regeneration by Centella asiatica in the journal of pharmacy and pharmacology

  • Regular poster presentations and neurology and pharmacognosy conferences.

  • Book chapter on “Botanicals: preparations, uses, quality issues and interactions” in a volume focusing on complementary medicines for neurological diseases.

  • Funding from Integria (Mediherb) to study Bacopa saponins in human plasma.

  • Continuing education lecture at American Association of Neurology conference, Hawaii, 2003.

  • Lecture to students on Behavioral Neuroscience course, OHSU, 2009



Research at Oregon’s Wild Harvest (OWH)

Summary: In my former role as Director of Research and Development, and presently as consultant at OWH, I have performed numerous research related activities. In 2004, I successfully raised a USDA small business grant to study the effects of drying methods on microbial load in organically farmed herbs. I also facilitated a collaborative project between the National College of Natural Medicine (NCNM) and OWH in which the immunological effects of herbs grown or processed at OWH were examined in humans. This led to a number of grant applications. I have also facilitated the establishment of a research agreement between OHSU and OWH for OWH to provide extracts of passionflower for a clinical trial to be conducted in epilepsy patients at OHSU. The development of research projects at OWH is an on-going activity.

Collaborations established: Collaborations between NCNM, OHSU and OWH have been established.

Funding: USDA, Helfgott Research institute

Outcomes:

  • Collaborations established with NCNM and OHSU

  • Two publications on immunological effects of herbs

  • Poster presentation at the American Society of Pharmacognosy (Corvallis, 2005)

  • Development of templates for non-disclosure and research collaboration agreements.



V/3 Other research related activities

My research and general expertise in therapeutic use of botanical medicines has led to:



  • Publications (see end list).

  • Invited contribution at 3 conferences in the USA in 1996 (sponsored by the Drug Information Association, the United States Pharmacopoeia and American Academy of Neurology respectively) dealing with quality control and standardisation of botanical medicines (phytopharmaceuticals)

  • Collaborative work with Dr Ed Croom, Co-ordinator of the Phytomedicines Project at the University of Mississippi in 1996 resulting in a joint publication on microscopical analysis of Ginkgo biloba leaf. The information has also been utilised in a United States Pharmacopoeial monograph on Ginkgo biloba leaf.

  • Consultancy work for the American Herbal Pharmacopoeia. I co-authored the therapeutic section for monographs of 3 important herbs (Vitex, Ginkgo, Garlic).

  • Membership of United States Pharmacopoeia Advisory Panel on Standards for Dietary Supplements and Natural Products.


V/4 Supervision of research

I have supervised many research projects at all levels (undergraduate, Masters, PhD, postdoctoral and sabbatical) since 1990. Approximate numbers are below:


Postdoctoral scientists, research assistants and overseas academics 5

PhD projects 9

MSc laboratory project 20

BPharm/MPharm final year laboratory/field project 12

European students (Norway, Austria, Germany) laboratory projects 8

Summer Vacation students’ laboratory projects 10

Non Pharmacy BSc projects at KCL (collaborative) 4

BPharm and MSc literature surveys 30

Final year projects from other institution (Non-KCL) 2

Mentoring interns at OHSU 5

Research assistants at OHSU 4

Details of PhD projects:

Nine PhD projects have been supervised since 1992. Two (Lau, Lin) both obtained the “Departmental Prize for the best PhD thesis” in their respective academic years. All students who have completed have obtained excellent career positions.


Investigation of plants used to treat vitiligo. PhD student: Miss Dania Kowalska, started October 1992. Withdrew after one year due to ill-health. Funding: Self + Glaxo
Pharmacological and phytochemical studies on the anti-diabetic properties of Momordica charantia PhD student: Clara Lau, started October 1994, submitted September 1998, degree awarded Dec 1998. Funding: EPSRC CASE (Lipha). Employed as a Lecturer in Pharmacognosy first at Bradford University and now Assistant Professor at the Chinese University of Hong Kong.
Screening and bioassay guided fractionation of selected plants used in the treatment of vitiligo.

PhD student: Zhixiu Lin, started October 1994, part-time PhD; degree awarded November 1999. Funding: Vitiligo Society and Institute of Chinese Medicine. Employed as a Lecturer in Traditional Chinese Medicine, first at the Middlesex University, UK and now Assistant Professor in Macau.


Biological and phytochemical studies on some traditional anti-diabetic plants.

PhD student: Sairavee Srijayanta, started November 1996, degree awarded July 2000.

Funding: Self + KCL bursary for Thai students awarded in 1998. First employed as a postdoctoral scientist with Oxford Natural Products, UK, now working for Johnson and Johnson, Thailand.
Studies on the mode of action and active components of Vernonia anthelmintica. PhD student: Miss Melanie Pires; started October 1997; degree awarded November 2001. Funding: Phytopharm plc. First employed as a postdoctoral scientist at King’s College (funded by Stiefel UK), now working with the Medicines and Healthcare Products Registration Authority, UK.
Structure-activity relationships of an alkaloidal simulant for melanocyte proliferation. PhD student: Mr Radhakrishnan Venkatasamy; started April 1999. Funding: Self + ORS award + BTG International. Degree awarded Jan 2004. Employed as a Posdoctoral scientist at King’s College London.
Investigation of some Malaysian plants used in the treatment of diabetes. PhD student: Mrs Hasenah Ali; started Sept 2001. Funding: The Malaysian Government. Degree awarded 2005.
Investigation of anti-diabetic plants using in vitro bioassays. PhD student: Miss Katie Bawden; started March 2001. Funding Merck Research Labs, USA. Degree awarded 2006.
Studies on Chinese and Ayurvedic anti-psoriatic plants using in vitro bioassays. . PhD student: Miss Catherine Chronnell; started Sept 2001. Stiefel UK. Anticipated completion date: 2007

1V/5 Grants and Contracts:
Patents

Treatment of Skin Disorders. (relating to vitiligo) – several patents filed in UK, PCT countries, USA, China, Canada. Some have been granted, others are pending. OHSU has now acquired this patent family.

Compositions for Nerve Regeneration (based on Centella asiatica). Filed June/July 2005. PCT/US2005/021150. Pending.

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